Treatment Effects Can Mimic Recurrent Extramammary Paget Disease in Perianal Skin.

The histologic differential diagnosis of perianal Paget disease includes malignant melanoma, pagetoid spread of squamous cell carcinoma, and secondary involvement by colorectal carcinoma. While consideration of these entities is useful when establishing a diagnosis, it does not apply when patients with Paget disease undergo surveillance for recurrent disease. Treatment of perianal Paget disease consists of a combination of surgical excision with skin grafts and topical chemotherapeutic agents that induce cytologic alterations in benign cells and simulate recurrent malignancy. To evaluate the therapy-related changes and possible diagnostic pitfalls in patients with Paget disease, we reviewed 412 posttreatment tissue samples from 3 women with primary perianal Paget disease who underwent wide excision, skin grafting, and topical 5-fluorouracil therapy. Biopsy samples from engrafted skin often displayed single and clustered cells with hyperchromatic nuclei dispersed in the deep epidermis. Similar cells were scattered throughout all levels of the epidermis in biopsy samples following topical chemotherapy. The abnormal cells were negative for cytokeratin 7 (CK7) and mucicarmine in both situations. Disease ultimately recurred in all patients; some Paget cells showed classic features with eosinophilic or mucinous cytoplasm and eccentric nuclei, whereas others were smaller with less conspicuous atypia. All Paget cells showed strong, membranous CK7 staining. In short, treatment of perianal Paget disease can elicit cytologic abnormalities in benign epithelial cells that simulate the cytologic features of recurrent disease, and can diminish the atypia of Paget cells. Immunohistochemical stains for CK7 can be helpful when evaluating surveillance samples from these patients.

Gastric Carcinomas With Lymphoid Stroma: An Evaluation of the Histopathologic and Molecular Features.

Gastric carcinoma with lymphoid stroma is an uncommon variant enriched for mutually exclusive Epstein-Barr virus (EBV) positivity and mismatch repair (MMR) deficiency. We performed this study to evaluate molecular alterations in this morphologically homogeneous subtype and compare them with 295 conventional gastric cancers analyzed in The Cancer Genome Atlas study. We identified 31 study cases and subjected them to in situ hybridization for EBV-encoded RNAs and assessment for MMR status. Immunostains for PD-L1, ß-catenin, and HER2 were performed; extracted DNA was sequenced with a Comprehensive Cancer Panel. Most study patients were older adult men with stage I or II disease (76%). Tumors were classified as EBV/MMR-proficient (MMR-P) (n=7), EBV/MMR deficient (n=12), and EBV/MMR-P (n=12). EBV/MMR-P tumors were usually located in the proximal stomach (83%) and showed heterogenous growth patterns with glandular differentiation (83%). Tumors in all groups showed numerous tumor infiltrating lymphocytes and PD-L1 expression, infrequent nuclear ß-catenin accumulation (10%), and lacked both membranous HER2 staining and HER2 amplification. EBV/MMR-deficient tumors showed significantly higher tumor mutation burden (P=0.001) and KRAS alterations (56%) compared with EBV/MMR-P tumors (9%, P=0.05). TP53 variants were more common among EBV/MMR-P tumors (82%) compared with EBV/MMR proficient (0%, P=0.01) and EBV/MMR-deficient (11%, P<0.01) tumors. Alterations in KRAS, ARID1A, PIK3CA, and TP53 followed similar patterns of distribution compared with The Cancer Genome Atlas dataset. We conclude that gastric carcinomas with lymphoid stroma show a spectrum of molecular changes and frequent PD-L1 expression, raising the possibility that this subgroup of tumors may be susceptible to checkpoint inhibitors and/or agents that target receptor tyrosine kinase-mediated signaling.

Evaluation of site-specific and seasonal variation in colonic mucosal eosinophils.

Several systemic disorders and gastrointestinal diseases may be associated with increased colonic mucosal eosinophils, which may vary in number throughout the normal colon. Some investigators have proposed that colonic eosinophilia reflects allergen exposure, although this hypothesis has never been validated, and values quantifying the number of mucosal eosinophils that can be regarded as a normal finding are lacking. The aims of this study were to determine the number of intramucosal eosinophils normally present throughout the colon and evaluate the relationship between colonic eosinophilia and seasonal allergen exposure. Eosinophils in the crypt epithelium and lamina propria were evaluated in 198 mucosal biopsy specimens obtained from the ascending (n = 98) and descending (n = 100) colon of patients with normal colonoscopic examinations. The cases were stratified into 12 groups, reflecting the months during which the samples were obtained, and the mean number of mucosal eosinophils was determined for each group. Daily air pollen counts were recorded, and the mean determined for each month. Fifty-five percent of mucosal biopsy specimens from the ascending colon contained eosinophils in the crypt epithelium, compared with only 5% of biopsy specimens from the descending colon (P < .001). Lamina propria eosinophils were, on average, 3 times more numerous in the ascending compared with the descending colon (P < .001). Mucosal eosinophils were slightly more numerous in samples obtained in April and May, corresponding to periods of highest pollen counts, but this relationship was not significant (P > .05). We conclude that intramucosal eosinophils are commonly present in the proximal colon but show only mild fluctuations with ambient allergen exposure.